This is the renewal application for PO1 HL-40962, "Biobehavioral Studies of Cardiovascular Disease." This Program Project studiers behavioral and psychobiologic attributes of individuals: (1) as potential etiological variables or markers for pathogenic processes in cardiovascular (CV) disease; and (2) as consequences of therapeutic interventions aimed at prevention or amelioration of CV risk. We propose four related research projects, supported by three Core Units. Investigators represent psychological and psychiatry, human and veterinary cardiology, neuropharmacology, neurobiology, epidemiology, genetics, primatology and biostatistics. Project 1 seeks to establish whether psychosocial, socio-environmental and lifestyle risk factors for CV disease are associated with inter-individual variability in central nervous system serotonergic responsivity, and if such responsivity may be predicted by genetic polymorphisms in serotonin system. Project 2 evaluates associations between central serotonergic responsivity and biological risk factors for atherosclerotic CV disease. Risk factors of interest in Project 1 include; hostility, depression, SES, social support, stress, diet, physical inactivity, smoking and alcohol use; and in Project 2: blood pressure, cardiac autonomic control, CV reactivity to stress, and visceral adiposity, insulin resistance and other components of the insulin resistance syndrome. Projects 1 and 2 are based on a community sample of 600 individuals who will be administered a neuropharmacologic challenge to assess central serotonergic responsivity. Project 3 evaluates therapeutic effects of the serotonergic agent, citalopram, on hostility and other behavioral risk factors, and biological markers of disease risk (serum lipids, insulin and glucose; autonomic balance and stress-related CV reactivity; platelet activation). Projects 1 and 2 also examine the factor exposure (carotid artery atherosclerosis, endothelium-mediated vasodilation of the brachial artery). Relatedly, Project 4 (at Wake Forest University) investigates social and ovarian influences on endothelial dysfunction and instrumentation support and development; data management statistical and participant recruitment services; and centralized administrative functions.